'Network' analysis of the brain may explain features of autism

A look at how the brain processes information finds a distinct pattern in children with autism spectrum disorders. Using EEGs to track the brain’s electrical cross-talk, researchers from Boston Children’s Hospital have found a structural difference in brain connections. Compared with neurotypical children, those with autism have multiple redundant connections between neighboring brain areas at the expense of long-distance links.

The study, using a “network analysis” like that used to study airlines or electrical grids, may help in understanding some classic behaviors in autism. It was published February 27 in BioMed Central’s open access journal BMC Medicine, accompanied by a commentary.

"We examined brain networks as a whole in terms of their capacity to transfer and process information," says Jurriaan Peters, MD, of the Department of Neurology at Boston Children’s Hospital, who is co-first author of the paper with Maxime Taquet, a PhD student in Boston Children’s Computational Radiology Laboratory. "What we found may well change the way we look at the brains of autistic children."

Peters, Taquet and senior authors Simon Warfield, PhD, of the Computational Radiology Laboratory and Mustafa Sahin, MD, PhD, of Neurology, analyzed EEG recordings from two groups of autistic children: 16 children with classic autism, and 14 children whose autism is part of a genetic syndrome known as tuberous sclerosis complex (TSC). They compared these readings with EEGs from two control groups—46 healthy neurotypical children and 29 children with TSC but not autism.

In both groups with autism, there were more short-range connections within different brain region, but fewer connections linking far-flung areas.

A brain network that favors short-range over long-range connections seems to be consistent with autism’s classic cognitive profile—a child who excels at specific, focused tasks like memorizing streets, but who cannot integrate information across different brain areas into higher-order concepts.

"For example, a child with autism may not understand why a face looks really angry, because his visual brain centers and emotional brain centers have less cross-talk," Peters says. "The brain cannot integrate these areas. It’s doing a lot with the information locally, but it’s not sending it out to the rest of the brain."

Ultrasound reveals autism risk at birth

Low-birth-weight babies with a particular brain abnormality are at greater risk for autism, according to a new study that could provide doctors a signpost for early detection of the still poorly understood disorder.

Led by Michigan State University, the study found that low-birth-weight newborns were seven times more likely to be diagnosed with autism later in life if an ultrasound taken just after birth showed they had enlarged ventricles, cavities in the brain that store spinal fluid. The results appear in the Journal of Pediatrics.

“For many years there’s been a lot of controversy about whether vaccinations or environmental factors influence the development of autism, and there’s always the question of at what age a child begins to develop the disorder,” said lead author Tammy Movsas, clinical assistant professor of pediatrics at MSU and medical director of the Midland County Department of Public Health.

“What this study shows us is that an ultrasound scan within the first few days of life may already be able to detect brain abnormalities that indicate a higher risk of developing autism.”

Movsas and colleagues reached that conclusion by analyzing data from a cohort of 1,105 low-birth-weight infants born in the mid-1980s. The babies had cranial ultrasounds just after birth so the researchers could look for relationships between brain abnormalities in infancy and health disorders that showed up later. Participants also were screened for autism when they were 16 years old, and a subset of them had a more rigorous test at 21, which turned up 14 positive diagnoses.

Ventricular enlargement is found more often in premature babies and may indicate loss of a type of brain tissue called white matter.

“This study suggests further research is needed to better understand what it is about loss of white matter that interferes with the neurological processes that determine autism,” said co-author Nigel Paneth, an MSU epidemiologist who helped organize the cohort. “This is an important clue to the underlying brain issues in autism.”

Prior studies have shown an increased rate of autism in low-birth-weight and premature babies, and earlier research by Movsas and Paneth found a modest increase in symptoms among autistic children born early or late.

Some Autism Behaviors Linked to Altered Gene

Scientists at Washington University School of Medicine in St. Louis have identified a genetic mutation that may underlie common behaviors seen in some people with autism, such as difficulty communicating and resistance to change.

An error in the gene, CELF6, leads to disturbances in serotonin, a chemical that relays messages in the brain and has long been suspected to be involved in autism.

The researchers identified the error in a child with autism and then, working in mice, showed that the same genetic alteration results in autism-related behaviors and a sharp drop in the level of serotonin circulating in the brain.

While the newly discovered mutation appears to be rare, it provides some of the first clues to the biological basis of the disease, the scientists report Feb. 13 in the Journal of Neuroscience.

“Genetically, autism looks very complicated, with many different genetic routes that lead to the disease,” says lead author Joseph D. Dougherty, PhD, an assistant professor of genetics at Washington University. “But it’s not possible to design a different drug for every child. The real key is to find the common biological pathways that link these different genetic routes and target those pathways for treatment.”

Autism is known to have a strong genetic component, but the handful of genes implicated in the condition so far explain only a small number of cases or make a small contribution to symptoms.

This led Dougherty and senior author Nathaniel Heintz, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, to speculate that some of the most common behavioral symptoms of autism may be caused by disruptions in a common biological pathway, like the one involved in serotonin signaling.

Yale researchers spot attention deficits in babies who later develop autism

Researchers at Yale School of Medicine are able to detect deficits in social attention in infants as young as six months of age who later develop Autism Spectrum Disorders (ASD). Published in the current issue of Biological Psychiatry, the results showed that these infants paid less attention to people and their activities than typically developing babies.

Katarzyna Chawarska, associate professor at the Yale Child Study Center, and her colleagues investigated whether six-month-old infants later diagnosed with ASD showed prodromal symptoms — early signs of ASD such as an impaired ability to attend to social overtures and activities of others. Before this study, it had not been clear whether these prodromal symptoms were present in the first year of life.

“This study highlights the possibility of identifying certain features linked to visual attention that can be used for pinpointing infants at greatest risk for ASD in the first year of life,” said Chawarska. “This could make earlier interventions and treatments possible.”

Autism Speaks Through Gene Expression

Autism spectrum disorders affect nearly 1 in 88 children, with symptoms ranging from mild personality traits to severe intellectual disability and seizures. Understanding the altered genetic pathways is critical for diagnosis and treatment. New work to examine which genes are responsible for autism disorders will be presented at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.

“Autism is the most inheritable of neurodevelopmental disorders,” explains Rajini Rao of Johns Hopkins University in Baltimore, Md., “but identifying the underlying genes is difficult since no single gene contributes more than a tiny fraction of autism cases.” Rather, she continues, “mutations in many different genes variably affect a few common pathways.”

A team of scientists at Johns Hopkins and Tel Aviv University in Israel looked at genetic variations in DNA sequence in the ion transporter NHE9 and found that autism-associated variants in NHE9 result in a profound loss of transporter function. “Altering levels of this transporter at the synapse may modulate critical proteins on the cell surface that bring in nutrients or neurotransmitters such as glutamate,” says Rao. “Elevated glutamate levels are known to trigger seizures, possibly explaining why autistic patients with mutations in these ion transporters also have seizures.”

A unique aspect of the team’s approach was that they exploited decades of basic research done in bacteria and yeast to study a complex human neurological disorder. First, the group at Tel Aviv University, led by Nir Ben-Tal, built structural models of NHE9 using a bacterial relative as a template, allowing the Rao laboratory at Johns Hopkins to use the simple baker’s yeast for screening the mutations. In the future, as genomic information becomes readily available for everyone, such easy, inexpensive, and rapid screening methods will be essential to evaluate rare genetic variants in autism and other disorders.

Rao and her team are optimistic about the potential benefits of their latest findings. “Although the research is still at an early stage, drugs that target the cellular pathways regulated by NHE9 could compensate for its loss of function and lead to potential therapy in the future,” Rao says. “These findings add a new candidate for genetic screening of at-risk patients that may lead to better diagnosis or treatment of autism.”

Researcher uncovers potential cause, biomarker for autism and proposes study to investigate theory

A New York-based physician-researcher from Touro College of Osteopathic Medicine, best known for his research into fertility and twinning, has uncovered a potential connection between autism and a specific growth protein that could eventually be used as a way to predict an infant’s propensity to later develop the disease. The protein, called insulin-like growth factor (IGF), is especially involved in the normal growth and development of babies’ brain cells. Based on findings of prior published studies, Touro researcher Gary Steinman, MD, PhD, proposes that depressed levels of this protein in the blood of newborns could potentially serve as a biomarker for the later development of autism. However, this connection, described below in greater detail, has never been directly studied. Steinman presents his exciting theory in the journal Medical Hypotheses.

IGF stimulates special cells in the brain to provide an essential insulating material, called myelin, around the developing nerves that is needed to efficiently transmit important messages about everything the brain controls — from physical functions such as movement to mental functions such as sensory perception, thinking and emotions. In the developing fetal and pediatric brain, myelin is also important for nerve fibers in one area of the brain to form proper pathways to other regions, allowing the body to hone functions over time. Insufficient IGF results in insufficient insulating material, as has been seen in brain biopsies of autistic individuals, and may impede proper pathway development. Steinman is proposing that this potential relationship between neonatal IGF levels and autism be directly studied.

"Autism is on the rise, especially in the last two decades — either because of environmental factors, expanded diagnostic criteria, or both. Yet almost nothing is currently known about the predisposing molecular and histological changes that differentiate a newborn destined to be neurologically normal from an autistic one," said Steinman.

Because no effective treatment or prevention for autism exists, research examining Steinman’s idea is critical, as it may hold the key to understanding the cause of this often devastating illness. In his article, Steinman proposes a study to investigate this hypothesis, and if this study supports his theory that identification of reduced IGF at birth is later followed by the appearance of autistic characteristics, then the subsequent development of a simple biomarker blood test is equally critical.